Lipopolysaccharide induces CXCL2/macrophage inflammatory protein-2 gene expression in enterocytes via NF-kappaB activation: independence from endogenous TNF-alpha and platelet-activating factor

Particulate matter (PM) metal content and bioavailability have been hypothesized to play a role in the health effects epidemiologically associated with PM exposure, in particular that associated with emission source PM. Using rat tracheal epithelial cells in primary culture, the present study compared and contrasted the acute airway epithelial effects of an emission source particle, residual oil fly ash (ROFA), with that of its principal constitutive transition metals, namely iron, nickel, and vanadium. Over a 24-h period, exposure to ROFA, vanadium, or nickel plus vanadium, but not to iron or nickel, resulted in increased epithelial permeability, decreased cellular glutathione, cell detachment, and lytic cell injury. Treatment of vanadium-exposed cells with buthionine sulfoximine further increased cytotoxicity. Conversely, treatment with the radical scavenger dimethylthiourea inhibited the effects in a dose-dependent manner. RT-PCR analysis of RNA isolated from ROFA-exposed rat tracheal epithelial cells demonstrated significant macrophage inflammatory protein-2 and interleukin-6 gene expression as early as 6 h after exposure, whereas gene expression of inducible nitric oxide synthase was maximally increased 24 h postexposure. Again, vanadium (not nickel) appeared to be mediating the effects of ROFA on gene expression. Treatment with dimethylthiourea inhibited both ROFA- and vanadium-induced gene expression in a dose-dependent manner. Corresponding effects were observed in interleukin-6 and macrophage inflammatory protein-2 synthesis. In summary, generation of an oxidative stress was critical to induction of the ROFA- or vanadium-induced effects on airway epithelial gene expression, cytokine production, and cytotoxicity.

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2,4-Dinitrofluorobenzene Modifies Cellular Proteins and Induces Macrophage Inflammatory Protein-2 Gene Expression via Reactive Oxygen Species Production in RAW 264.7 Cells

Immunological Investigations ◽

10.1080/08820130802667499 ◽

2009 ◽

Vol 38 (2) ◽

pp. 132-152 ◽

Cited By ~ 12

Author(s):

Dongbum Kim ◽

Young-Jin Kim ◽

Jae-Nam Seo ◽

Jinho Kim ◽

Younghee Lee ◽

...

Keyword(s):

Gene Expression ◽

Reactive Oxygen Species ◽

Reactive Oxygen Species Production ◽

Cellular Proteins ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Oxygen Species ◽

Inflammatory Protein ◽

Species Production ◽

Macrophage Inflammatory Protein

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Inflammatory microcrystals differentially regulate the secretion of macrophage inflammatory protein 1 and interleukin 8 by human neutrophils: a possible mechanism of neutrophil recruitment to sites of inflammation in synovitis.

Journal of Experimental Medicine ◽

10.1084/jem.182.6.2019 ◽

1995 ◽

Vol 182 (6) ◽

pp. 2019-2025 ◽

Cited By ~ 78

Author(s):

M Hachicha ◽

P H Naccache ◽

S R McColl

Keyword(s):

Inflammatory Cytokines ◽

Interleukin 8 ◽

Tnf Alpha ◽

Human Neutrophils ◽

Calcium Pyrophosphate Dihydrate ◽

Pathological State ◽

Dependent Manner ◽

Gm Csf ◽

Inflammatory Protein ◽

Macrophage Inflammatory Protein

Human neutrophils at inflammatory sites may be an important source of the chemotactic cytokines macrophage inflammatory protein 1 alpha (M1P-1 alpha; a C-C chemokine) and interleukin 8 (IL-8; a C-X-C chemokine). In this study, we show that the inflammatory microcrystals monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPPD), the major mediators of gout and pseudogout, differentially regulate the production of these two chemokines by human neutrophils. Both MSU and CPPD increased the secretion of IL-8 by neutrophils in a dose- and time-dependent manner, but had no effect on that of MIP-1 alpha. Since inflammatory cytokines are likely to be present in the synovium during crystal-induced inflammation, we examined the interaction between TNF-alpha and GM-CSF and the crystals. Both TNF-alpha and GM-CSF stimulated IL-8 production; however, only TNF-alpha exerted a significant effect on MIP-1 alpha secretion in neutrophils. IL-8 production induced by TNF-alpha and GM-CSF was synergistically enhanced in the presence of MSU or CPPD, whereas MIP-1 alpha secretion induced by TNF was completely inhibited in the presence of either MSU or CPPD. Interestingly, no interaction between the crystals and the inflammatory cytokines was observed with respect to synthesis of the C-X-C chemokine MGSA in neutrophils. These results suggest that the combination of TNF-alpha and GM-CSF with MSU or CPPD will lead to the production of IL-8 by neutrophils and abolish the release of MIP-1 alpha, an event that will theoretically lead to recruitment of neutrophils but not mononuclear cells. These results are in accordance with the pathological state of gout and pseudogout, where the predominant inflammatory cell is the neutrophil.

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Hypoxia induces macrophage inflammatory protein‐2 (MIP‐2) gene expression in murine macrophages via NF‐κB: the prominent role of p42/ p44 and PI3 kinase pathways

The FASEB Journal ◽

10.1096/fj.03-0991fje ◽

2004 ◽

Vol 18 (10) ◽

pp. 1090-1092 ◽

Cited By ~ 57

Author(s):

A. Zampetaki ◽

S. A. Mitsialis ◽

J. Pfeilschifter ◽

S. Kourembanas

Keyword(s):

Gene Expression ◽

Pi3 Kinase ◽

Murine Macrophages ◽

Inflammatory Protein ◽

Macrophage Inflammatory Protein

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Transforming growth factor-beta 1, macrophage inflammatory protein-1 alpha, and interleukin-8 gene expression is lower in stimulated human neonatal compared with adult mononuclear cells

Blood ◽

10.1182/blood.v84.1.118.bloodjournal841118 ◽

1994 ◽

Vol 84 (1) ◽

pp. 118-124 ◽

Cited By ~ 2

Author(s):

M Chang ◽

Y Suen ◽

SM Lee ◽

D Baly ◽

JS Buzby ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Mononuclear Cells ◽

Transforming Growth Factor ◽

Tgf Beta ◽

Altered Expression ◽

Inflammatory Protein ◽

Growth Factor Beta ◽

Macrophage Inflammatory Protein

Hematopoiesis is developmentally immature in the newborn compared with the adult. Diminished gene expression of several positive hematopoietic regulators has been observed in activated cord compared with adult peripheral blood mononuclear cells (MNC; Cairo et al. Pediatr Res, 30:362, 1991 and Cairo et al, Pediatr Res, 31:574, 1992). However, altered expression of negative hematopoietic regulators during states of increased demand may also contribute to the pathogenesis of newborn dyshematopoiesis. To test this hypothesis, we measured protein levels of transforming growth factor-beta 1 (TGF-beta 1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the conditioned media of human umbilical cord and adult MNC using specific enzyme-linked immunosorbent assays. There was significantly less TGF-beta 1 in culture supernatants of cord versus adult MNC after 24, 72, and 120 hours of stimulation (P < .05), and significantly less MIP-1 alpha in cord versus adult supernatants after 72 hours and 120 hours of stimulation (P < .01). We then examined the mRNA expression of the negative regulators TGF-beta 1, MIP-1 alpha, and interleukin-8 (IL-8) in cord and adult MNC using Northern blot hybridization followed by quantitative densitometry. Cord MNC expressed significantly less TGF- beta 1 mRNA than adult MNC 6 hours and 72 hours after stimulation (P < .001). Cord MNC expressed significantly less MIP-1 alpha mRNA than adult MNC 6 hours (P < .01), 24 hours (P < .001), and 72 hours after stimulation (P < .001). Cord MNC also expressed significantly less IL-8 mRNA than adult MNC 6 hours after stimulation (P < .001). Therefore, decreased mRNA accumulation appears to coincide with reduced cytokine expression in the activated cord MNC. There were no significant differences in the transcription rates determined by nuclear run-on assay of either the TGF-beta 1 or MIP-1 alpha gene in cord versus adult MNC after 6 hours of stimulation, suggesting that the reduced TGF-beta 1 and MIP-1 alpha mRNA in activated cord MNC may be secondary to alteration in posttranscriptional regulation. The present results, together with those of our previous studies, suggest that the altered expression of both positive and negative hematopoietic regulators may be involved in the immaturity of host defense in human neonates.

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C/EBP, NF-kappa B, and c-Ets family members and transcriptional regulation of the cell-specific and inducible macrophage inflammatory protein 1 alpha immediate-early gene

Molecular and Cellular Biology ◽

10.1128/mcb.13.9.5276-5289.1993 ◽

1993 ◽

Vol 13 (9) ◽

pp. 5276-5289

Author(s):

M Grove ◽

M Plumb

Keyword(s):

Gene Expression ◽

Dna Binding ◽

Family Members ◽

Early Gene ◽

Proximal Promoter ◽

Nf Kappa B ◽

Inflammatory Protein ◽

Ets Family ◽

Alpha Gene ◽

Macrophage Inflammatory Protein

Macrophage inflammatory protein 1 alpha (MIP-1 alpha) cytokine gene expression is restricted to a limited number of cells of hemopoietic origin and is rapidly and transiently induced by serum and endotoxin in macrophages. A single nuclear DNase I-hypersensitive site, which maps to the proximal promoter of the MIP-1 alpha gene, was identified in macrophage cells but was absent in cells which do not express basal levels of MIP-1 alpha mRNA. The proximal promoter sequences (+36 to -220 bp) are sufficient to confer cell-specific and inducible transcription in transfection assays. In vitro DNA-binding studies revealed five major nuclear protein binding sites in the proximal promoter which bind C/EBP, NF-kappa B, and/or c-Ets family members. Cell-specific differences in DNA binding by members of the NF-kappa B and c-Ets families correlate with the cell-specificity of MIP-1 alpha gene expression and the chromosomal conformation of the promoter. Changes in promoter binding by members of the C/EBP and NF-kappa B families correlate with the transcriptional up-regulation observed in serum- or endotoxin-stimulated macrophages in functional studies.

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Induction of Macrophage-Inflammatory Protein-3α Gene Expression by TNF-Dependent NF-κB Activation

The Journal of Immunology ◽

10.4049/jimmunol.168.11.5621 ◽

2002 ◽

Vol 168 (11) ◽

pp. 5621-5628 ◽

Cited By ~ 75

Author(s):

Shinichi Sugita ◽

Tomoko Kohno ◽

Kazuo Yamamoto ◽

Yoshitaka Imaizumi ◽

Hisayoshi Nakajima ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Protein ◽

Macrophage Inflammatory Protein

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Acid-induced Lung Injury

Anesthesiology ◽

10.1097/00000542-200312000-00013 ◽

2003 ◽

Vol 99 (6) ◽

pp. 1323-1332 ◽

Cited By ~ 19

Author(s):

Lilly Madjdpour ◽

Sita Kneller ◽

Christa Booy ◽

Thomas Pasch ◽

Ralph C. Schimmer ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Expression Pattern ◽

Binding Activity ◽

Pyrrolidine Dithiocarbamate ◽

Inflammatory Protein ◽

Nf Kappab ◽

Macrophage Inflammatory Protein

Background Aspiration of acidic gastric contents leads to acute lung injury and is still one of the most common clinical events associated with acute lung injury. This study was performed to assess acid-induced lung inflammation in vitro and in vivo with respect to the time pattern of activated transcription factor nuclear factor-kappaB (NF-kappaB) and proinflammatory molecules. Methods L2 cells (alveolar epithelial cells) were exposed for various periods to a medium with a pH of 6. In the in vivo model, 1 ml/kg of 0.1 n acidic solution was instilled into the lungs of rats. NF-kappaB binding activity and expression pattern of inflammatory mediators were determined. Blocking studies were performed with the NF-kappaB inhibitor pyrrolidine dithiocarbamate. Results In vitro NF-kappaB binding activity showed a biphasic expression pattern with a first peak at 1 h and a second one at 6-8 h. In acid-injured rat lungs, NF-kappaB binding activity was confirmed in a biphasic manner with a first increase at 0.5-2 h (608 +/- 93% and 500 +/- 15%, respectively, P < 0.05) and a second peak at 8 h (697 +/- 35% increase, P < 0.005). Whole lung mRNA for macrophage inflammatory protein-1beta and macrophage inflammatory protein-2 showed a similar expression pattern, which could explain the biphasic neutrophil recruitment. Intratracheal pyrrolidine dithiocarbamate attenuated lung injury as evidenced by a reduction of neutrophil accumulation and expression of inflammatory mediators. Conclusions These data suggest that NF-kappaB binding activity plays a key role in molecular and cellular events in acid-induced lung injury.

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